Controling stem cell proliferation - CKIs at work

The cyclin-dependent kinase inhibitors or CKIs are well recognized as intrinsic regulators of the cell cycle. Here, we discuss recent data implicating their activity in restraining adult stem cell self-renewal, and the role that proteins regulating CKI expression play in this process

Emerging roles of Polycomb silencing in X-inactivation and stem cell maintenance

Maintenance of cell identity and cell fate depends on the tight regulation of gene expression patterns in correct time and space. Two families of proteins, the trithorax group (trxG) and the Polycomb group (PcG), use epigenetic mechanisms to faithfully ensure that designated genes are maintained on or off throughout the life of the organism, This maintenance function is imperative to allow the proper development of an organism from a single cell to an organized combination of multifunctional cells. Here, we briefly review the advances achieved in recent years aimed at understanding how members of PcG and trxG function (for more in-depth reviews, see Otte and Kwaks 2003; Pirrotta et al. 2003; Lund and van Lohuizen 2004; Valk-Lingbeek et al. 2004). Particularly, we will discuss methods that can be employed to uncover additional target genes regulated by PcG and/or trxG families. Additionally, we will focus on recent results linking PcG regulation with X-inactivation and with stem cell biology

Increasing p16(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing

Mammalian ageing is associated with reduced regenerative capacity in tissues that contain stem cells(1,2). It has been proposed that this is at least partially caused by the senescence of progenitors with age(3,4); however, it has not yet been tested whether genes associated with senescence functionally contribute to physiological declines in progenitor activity. Here we show that progenitor proliferation in the subventricular zone and neurogenesis in the olfactory bulb, as well as multipotent progenitor frequency and self-renewal potential, all decline with age in the mouse forebrain. These declines in progenitor frequency and function correlate with increased expression of p16(INK4a), which encodes a cyclin-dependent kinase inhibitor linked to senescence(5). Ageing p16(INK4a)-deficient mice showed a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis, and the frequency and self-renewal potential of multipotent progenitors. p16(INK4a) deficiency did not detectably affect progenitor function in the dentate gyrus or enteric nervous system, indicating regional differences in the response of neural progenitors to increased p16(INK4a) expression during ageing. Declining subventricular zone progenitor function and olfactory bulb neurogenesis during ageing are thus caused partly by increasing p16(INK4a) expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62695/1/nature05091.pd